Very few clinical treatments are available to reduce the damage and subsequent dysfunction following traumatic brain injury (TBI). This is partially due to the fact that cellular mechanisms of dysfunction and death are yet to be fully elucidated. To better understand the various mechanical, electrical, and chemical events during neural injury, and to establish cell tolerances to mechanical insult, it is critical to establish injury models that precisely control cell strain, the physical event that initiates the trauma cascade.

To this end, this thesis project focuses on the creation of a novel single-cell injury model of TBI. The implementation of the model requires the development of a novel injury device that allows direct micro-interfacing with neural environments.

This device consists of a high–resolution micro-electro-mechanical-system (MEMS) microtweezer microactuator that is compatible with aqueous environments and can be proximally positioned within neural tissue and neural cultures. This microtweezer is constructed using traditional photolithography and micromachining processes, and is packaged into a custom machined stainless steel luer needle. The packaged device is controllable by a custom developed software-automated controller that incorporates a high precision linear actuator and utilizes a modular luer-based docking interface.

Following mechanical characterization and biocompatibility assessment, the microtweezer system was used to induce mechanical insults with prescribed strain and strain rate onto the somata of primary cortical neurons in 2D culture. Real-time injury-induced intracellular calcium change and post-injury neuronal plasma membrane permeability were evaluated. Membrane permeability is a significant contributor to secondary injury cascades during TBI. By evaluating cellular response to mechanical input using models like these, strain and strain rate input tolerance criteria can be used to determined thresholds for membrane integrity, cellular injury, and death. These findings provide a new platform for traumatic single-cell injury and can be integrated with results from bulk injury models, where the entire culture or tissue is injured, to gain a better understanding of the collective cell response to injury